Premature ovarian failure

Premature ovarian failiure may occur due to auto-immune disease or as an isolated 'premature menopause'. The diagnosis is also known as primary ovarian failure or primary gonadal failure.

Baseline investigations - all patients

Full blood count

Useful indicator of general health and underlying disease. Macrocytosis may occur with associated B12 deficiency.

Urea and electrolytes

Useful indicator of general health and underlying disease.

Hyperkalaemia and hyponatraemia may occur in glucocorticoid deficiency.

Vitamin B12 levels

Premature ovarian failure may be associated with conditions such as pernicious anaemia and coeliac disease which may affect vitamin B12 absorption. 

Liver function test

Useful indicator of general health and underlying disease.

Bone profile

Useful indicator of general health and underlying disease.

Hypercalcaemia may occur with glucocorticoid deficiency.

Baseline pituitary function


Estrodial and sex hormone binding globulin

Ensure that all interfering medication, for example the contraceptive pill, has been stopped for six weeks prior to assessment. If the patient is still menstruating, perform this assessment in the early follicular phase.


Luteinising hormone, follicle stimulating hormone

Elevated LH and FSH indicate primary gonadal failure. Amenorrhoea, with a low estrodiol level and a low or normal LH and FSH, indicates an alternative pathology. Interfering medications, low BMI, excessive exercise, or pituitary dysfunction should all be considered in this case.


Prolactin

Hyperprolactinaemia frequently presents with secondary amenorrhoea.

Serum prolactin is affected by many factors, for example stress, nipple stimulation, interfering medications and PCOS, and so should always be repeated on at least two occasions. 

Elevated prolactin levels should also prompt the PEG precipitation test to determine whether this is biologically active or the inactive 'macroprolactin'.


Thyroid stimulating hormone, free thyroxine

Thyrotoxicosis commonly causes oligomenorrhoea or secondary amenorrhoea mimicking hopogonadism.

Thyroid dysfunction is also more common in people with premature ovarian failure.


9am cortisol

This is required in patients with hypogonadotropic hypogonadism to detect possible pituitary failure.

It is also useful in patients with premature ovarian failure due to the increased incidence of Addison's disease with auto-immune aetiology.

Levels above 590nmol/l exclude glucocorticoid deficiency in all cases. Patients with pituitary disease and levels below this may require formal assessment for ACTH reserve, for example with an insulin stress test or glucagon test. Patients with premature ovarian failure and suggestive features of Addison's disease will require a synacthen test.


Growth hormone, insulin like growth factor I

These are only required with confirmed hypogonadotropic hypogonadism and suspected pituitary disease.

Very low IGF-I levels alone are not diagnostic for GH deficiency but are a useful screen indicating potential pituitary dysfunction.

Auto-antibody screen

Premature ovarian failure is frequently auto-immune in origin although ovarian antibodies are not always positive.

It is frequently associated with other auto-immune conditions. It is therefore useful to document thyroid antibodies and a coeliac screen at baseline to aid future management.

Bone densitometry scan

This should be considered in all patients with long standing hypogonadism. It may be useful to repeat after five years of treatment.

Further investigations - selected cases only

Vitamin D

Low serum vitamin D levels strengthen the case for vitamin D replacement therapy in patients with osteoporosis of any cause.

Pelvic ultrasound scan

This can be helpful to assess uterine size prior to considering fertility treatment and pregnancy.

This is also useful to perform in patients presenting with absent or delayed puberty to assess uterine and anatomy and confirm whether ovaries are present.

Karyotype

This should be performed at presentation in patients with absent puberty, in all patients with suspected Turner’s syndrome and in selected cases of secondary amenorrhoea with hypogonadotropic hypogonadism.

It is not usually necessary in patients with confirmed hypergonadotropic hypogonadism or premature ovarian failure.